Study: optogenetics used to stop rats binge drinking

A team of neurobiologists taught rats to binge on alcohol, then watched as each refused a drink when their dopamine-controlling neurons were stimulated.

The team from Wake Forest University and the University at Buffalo (UB) managed to convince the rats to go cold turkey using optogenetics, where specific neurons are made light-sensitive using proteins so they can be easily stimulated using implanted optic fibres.

“For decades, we have observed that particular brain regions light up or become more active in an alcoholic when he or she drinks or looks at pictures of people drinking, for example, but we didn’t know if those changes in brain activity actually governed the alcoholic’s behaviour,” lead author on the paper and assistant professor of pharmacology and toxicology at UB Caroline Bass said.

It’s well known that dopamine is directly linked to alcoholism, being a control system that adjusts feelings associated with reward and pleasure. Levels of dopamine usually appear raised in anyone hooked on addictive substances. But what the Wake Forest-UB team found was that stimulating the correct neurons not only reversed binge drinking behaviour, it prevented it even well after stimulation of the neurons ceased.

After getting the rats hooked on binge drinking (they would comply when a supply was provided) the team used a virus to deliver the light-responsive protein Channelrhodopsin-2 (ChR2) to the dopamine-controlling neurons.

“I created a virus that will make this protein only in dopaminergic neurons,” said Bass.

An optical fibre was then implanted into the region, which would act as a switch to turn dopamine release on and off in a more precise way than an electrical current ever could, since it only acts where the protein is.

“ChR2 was selectively expressed on the ventral tegmental area dopamine cells and delivery of blue light pulses induced dopamine release,” wrote the team in a paper published in Frontiers in Behavioural Neuroscience.

“By stimulating certain dopamine neurons in a precise pattern, resulting in low but prolonged levels of dopamine release, we could prevent the rats from binging,” said Bass. “The rats just flat out stopped drinking.”

“These data provide us with concrete direction about what kind of patterns of dopamine cell activation might be most effective to target alcohol drinking,” adds coauthor Evgeny Budygin. What optogenetics is enabling, is more precise mapping of the brain so that researchers can identify and plot the cause and affect of a whole host of behaviours, as they have attempted to do here.

Bass is hopeful the brain mapping they have achieved with this study could not only help in identifying the neural pathways that control alcoholism in humans, but also in understanding and eventually treating Parkinson’s disease, where a region of the brain containing dopamine neurons degenerates.

“We can target dopamine neurons in a part of the brain called the nigrostriatal pathway, which is what degenerates in Parkinson’s disease. If we could infuse a viral vector into that part of the brain, we could target potentially therapeutic genes to the dopamine neurons involved in Parkinson’s. And by infusing the virus into other areas of the brain, we could potentially deliver therapeutic genes to treat other neurological diseases and mental illnesses, including schizophrenia and depression.”

It’s quite a leap from preventing rats from binge drinking. But it’s a step on the path to mapping the complexities of all kinds of neurological disorders.